Search PubMed⌕ Search

Biomedical subjects

J M Davis

Publications and source records attributed to J M Davis.

At least 253 records · Page 14Linked to original sources

Beta-receptor responsiveness after desipramine treatment.

To examine whether a tricyclic antidepressant affects the functional response to a beta-receptor agonist in man, the response of heart rate, blood pressure, and plasma cAMP to isoproterenol was measured in 14 normal controls taking 75 mg desipramine daily. Desipramine significantly increased the bolus dose of isoproterenol needed to increase heart rate by 25 bpm at 14-30 days but not at 3-8 days. During infusions of isoproterenol, the increase in systolic blood pressure was blunted at both 3-8 days and 14-30 days, while the decrease in diastolic blood pressure was unaffected. Blood pressure findings were not affected by preadministration of bethanechol. In ten controls, isoproterenol infusions increased plasma cAMP, but this was unaffected by desipramine treatment. These findings suggest a decrease in the functional response of beta 1, but not beta 2, receptors after treatment with desipramine.

Adult↗

Platelet serotonin-2 receptors in schizophrenia: effects of illness and neuroleptic treatment.

To examine the role of serotonin2 (5-hydroxytryptamine2, 5-HT2) receptors in schizophrenia, we determined the binding indices of 5-HT2 receptors using 125I-lysergic acid diethylamide (LSD) as the radioligand in platelets obtained from 40 normal control subjects and 42 drug-free schizophrenic patients. We also examined the effect of neuroleptic drug treatment on the binding parameters (Bmax and Kd) of 5-HT2 receptors in platelets of schizophrenic patients. We observed that the Bmax of 125I-LSD binding in platelets of schizophrenic patients was significantly higher than in platelets of normal subjects. There was no significant difference, however, between the Kd of 125I-LSD binding in platelets of schizophrenic patients and normal control subjects. Furthermore, we found no correlation between Brief Psychiatric Rating Scale scores and either Bmax or Kd of 125I-LSD binding at the end of the drug washout period. We also observed that neither treatment with haloperidol nor treatment with thiothixine caused significant changes in Bmax and Kd of 125I-LSD binding in platelets of schizophrenic patients. However, both fluphenazine and trifluoperazine did significantly increase the Bmax of 125I-LSD binding without any significant change in the Kd values in platelets of schizophrenic patients. Our results thus suggest that platelet 5-HT2 receptors are increased in schizophrenia and that chronic treatment with fluphenazine and trifluoperazine, but not haloperidol or thiothixine, further increases the 5-HT2 receptor binding sites in platelets of schizophrenic patients.

Adult↗

Developmental patterns of duration discrimination.

The purpose of this study was to determine whether the auditory perceptual abilities of children are characterized by an age-related improvement in duration discrimination. Forty children, ages 4 to 10 years, and 10 adults served as subjects. Difference limens were obtained using a 350-msec broadband noise burst as the standard stimulus in a three-interval forced-choice paradigm. Data were characterized by significant differences between the performances of the 4-, 6-, and 8-year-olds and those of the adults. Acquisition of adult-like discrimination performance was demonstrated between the ages of 8 and 10 years.

Acoustic Stimulation↗

Serotonergic agonists and antagonists affect endurance performance in the rat.

The purpose of this experiment was to examine the effects of administration of serotonergic (5-HT) agonist and antagonist drugs on run-time to exhaustion (RUN-EXH) in male and female rats. RUN-EXH was reduced (p < 0.05) in a dose related manner by increasing dosages of quipazine dimaleate (QD: general 5-HT agonist) (0-5 mg.kg-1 i.p.) administered immediately prior to exercise (treadmill running at 20 m.min-1 and 5% grade). Conversely, RUN-EXH was increased (p < 0.05) by the greatest dosage of LY 53,857 (LY: 5-HT1C and 5-HT2 antagonist) (1.5 mg.kg-1 i.p.). Drug effects were similar in male and female rats. The negative effects of QD administration on RUN-EXH were not attenuated by administration of the peripherally restricted antagonist, xylamidine tosylate (up to 200 ug.kg-1 i.p.). The results of this investigation indicated that fatigue during prolonged exercise can be influenced by direct pharmacological administration of a serotonergic agonist and antagonist and that the mechanisms underlying these effects are likely to be central (brain) in nature.

Amidines↗

Comparison of progenitor cell concentration techniques: continuous flow separation versus density-gradient isolation.

Bone marrow harvests were processed using two techniques; 20 mononuclear cell concentrations (MNC) were prepared on the COBE Spectra and compared to 10 light-density cell fractions isolated using the COBE 2991. Both procedures recovered essentially the same percentage of nucleated cells (22 versus 21%) and gave progenitor cell recoveries of 132 and 100% of the CFU-GM and 101 and 104% of the CD34+ cells in the MNC and light-density products, respectively. The advantage of the Spectra MNC concentrate is that it was prepared with reagents approved for injection by the Food and Drug Administration. However, the average hematocrit on the MNC concentrate was 4%, while it was unmeasurable in the light-density cell fractions. This difference is significant only when bone marrows require purging with 4-hydroperoxycyclophosphamide or erythrocytes otherwise interfere with processing. The Spectra procedure recovered a larger percentage of MNC cells and had less contamination with mature granulocytes than did the density-gradient technique. When erythrocytes do not affect the bone marrow processing protocol, a Spectra MNC concentrate is a safe substitute for a light-density cell preparation.

Adult↗

The use of Texas Scottish-Rite instrumentation in idiopathic scoliosis. A preliminary report.

The Texas Scottish-Rite instrumentation (TSRH) is a new system for the correction of spinal deformities that uses smooth rods and hooks stabilized to the rod with a three-point interference fit. This obviates the need for the break-off hex bolts and should make for easier removal and/or revision. Twenty-three patients with TSRH instrumentation were followed for an average of 18 months after surgery. The major scoliotic curve was corrected an average of 49% with the compensatory curve averaging 37% correction. Loss of thoracic kyphosis was less than 9 degrees although it increased on average 8 degrees in those patients where kyphosis was improved. There were no acute complications, but late complications included four cases of hook pull-out. Results are comparable to those found with the CD instrumentation. The TSRH instrumentation is an attractive alternative in scoliosis surgery, particularly because of the relative ease in which revision surgery may be performed.

Adolescent↗

Iron status of female runners.

This study was designed to observe iron status and prevalence of iron deficient conditions in adult female habitual runners (n = 111) and inactive females of comparable age (n = 65). The runners were significantly lower (p < .05) than the reference group in mean serum ferritin (SF), total iron binding capacity, and red blood cell count, but significantly higher (p < .05) in mean corpuscular hemoglobin. The groups did not differ significantly in hemoglobin concentration, hematocrit, serum iron, percent saturation of transferrin, or red cell protoporphyrin. Chi square analysis indicated that iron depletion (SF < 20 ng.ml-1) was significantly more prevalent (p < .005) in the runners than in the controls. Anemia was extremely rare in both groups. A multiple regression analysis revealed significant negative associations between serum ferritin and coffee/tea intake (p < .001) and running activity (p < .05). These results indicate that habitual runners, as compared with inactive women, are at increased risk for iron deficient states but that full-blown anemia is a rare consequence of this deficient iron status.

Adult↗

Effects of intracranial self-stimulation on selected physiological variables in rats.

The purpose of this investigation was to characterize selected metabolic, cardiovascular, and hormonal responses to reinforcing intracranial self-stimulation (ICSS) of the ventral tegmental area (VTA) in rats. Twenty male Sprague-Dawley rats were stereotaxically implanted with bipolar electrodes aimed at the VTA of the brain. Rats were trained to lever-press for ICSS for 1 wk. While they adapted to the experimental environment by sitting in a metabolic operant chamber, they were connected to the electrode cable but did not lever-press. All animals were instrumented with arterial catheters. Rats receiving contingent stimulation (C-St; n = 10) performed 30 min of lever pressing in the metabolic operant chamber for reinforcing brain stimulation. Oxygen consumption (VO2), heart rate (HR), mean arterial pressure (MAP), and rectal temperature (Trec) increased with the onset and continuation of contingent brain stimulation over 30 min (P < 0.05). In addition, plasma norepinephrine (NE), epinephrine (Epi), and corticosterone increased significantly above resting values in C-St rats (P < 0.05). Five animals received investigator-delivered reinforcing brain stimulation (noncontingent stimulation; NC-St), with MAP, HR, VO2, NE, and Epi increasing significantly above resting values (P < 0.05). Trec and corticosterone were not responsive to noncontingent brain stimulation. With the exception of HR, nonstimulated controls (n = 5) did not experience increases above resting values in any of the variables measured. The responses suggest that contingent brain stimulation reward elicits heightened sympathetic arousal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prophylactic effects of recombinant human superoxide dismutase in neonatal lung injury.

To determine if recombinant human Cu-Zn superoxide dismutase (rhSOD) would prevent acute lung injury caused by hyperoxia and barotrauma, 26 newborn piglets were studied. Ten piglets were hyperventilated (arterial PCO2 15-20 Torr) with 100% O2 for 48 h. A second group received identical treatment for 4 h (n = 2) or 48 h (n = 8) but was given 5 mg/kg of rhSOD intratracheally at time 0. Six piglets were normally ventilated (arterial PCO2 40-45 Torr) for 48 h with 21% O2. Pulmonary function and tracheal aspirates were examined at time 0 and at 24 and 48 h, and bronchoalveolar lavage was performed at 48 h. In piglets treated with hyperoxia and hyperventilation, lung compliance decreased 42%, and tracheal aspirates showed an increase in neutrophil chemotactic activity (32%), total cell counts (135%), elastase activity (93%), and albumin concentration (339%) over 48 h (P < 0.05). All variables were significantly lower in rhSOD-treated piglets and comparable to normoxic control values. Surfactant remained active in all groups. Immunohistochemistry demonstrated that at 48 h significant rhSOD was distributed homogeneously in terminal airways. Adding rhSOD to tracheal aspirates of hyperoxic hyperventilated piglets did not alter neutrophil chemotaxis, suggesting that rhSOD protected the lung by reducing the production of chemotactic mediators. Results indicate that acute lung injury caused by 48 h of hyperoxia and hyperventilation is significantly ameliorated by prophylactic intratracheal administration of rhSOD.

Animals↗

Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue.

Pharmacological manipulation of brain serotonergic [5-hydroxytryptamine (5-HT)] activity affects run time to exhaustion in the rat. These effects may be mediated by neurochemical, hormonal, or substrate mechanisms. Groups of rats were decapitated during rest, after 1 h of treadmill running (20 m/min, 5% grade), and at exhaustion. Immediately before exercise rats were injected intraperitoneally with 1 mg/kg of quipazine dimaleate (QD; a 5-HT agonist), 1.5 mg/kg of LY 53857 (LY; a 5-HT antagonist), or the vehicle (V; 0.9% saline). LY increased and QD decreased time to exhaustion (approximately 28 and 32%, respectively; P < 0.05). At fatigue, QD animals had greater plasma glucose, liver glycogen, and muscle glycogen concentrations but lower plasma free fatty acid concentration than did V and LY animals (P < 0.05). In general, plasma corticosterone and catecholamine levels during exercise in QD and LY rats were similar to those in V rats. Brain 5-HT and 5-hydroxyindole-3-acetic acid concentrations were higher at 1 h of exercise than at rest (P < 0.05), and the latter increased even further at fatigue in the midbrain and striatum (P < 0.05). Brain dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were higher at 1 h of exercise (P < 0.05) but were similar to resting levels at fatigue. QD appeared to block the increase in DA and DOPAC at 1 h of exercise, and LY prevented the decrease in DA and DOPAC at fatigue (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Exercise training alters cardiovascular and hormonal responses to intracranial self-stimulation.

Both reinforcing intracranial self-stimulation (ICSS) and physical exercise result in heightened cardiovascular and endocrine responses. This study compared the cardiovascular and endocrine responses to ICSS in rats after either chronic ICSS or treadmill running. Male rats (n = 35) were implanted with bipolar electrodes aimed at the ventral tegmental area of the brain, and those that performed vigorous lever pressing for ICSS (> 50 presses/min; n = 30) were counter balanced into three groups: chronic ICSS (PRESS), chronic run training (RUN), or sedentary controls (CONT). PRESS, RUN, and CONT rats performed ICSS, ran on a motorized treadmill, or sat quietly in cages for 30 min/day, 5 day/wk, for 12 wk, respectively. All animals then performed 30 min of lever pressing for ICSS and were immediately killed. Oxygen consumption, heart rate, blood pressure, rectal temperature, and plasma norepinephrine, epinephrine, and corticosterone increased (P < 0.05) for all groups during lever pressing. PRESS rats did not differ from CONT rats for any variable studied. However, heart rate was lower and oxygen consumption, norepinephrine, and corticosterone were higher in RUN than in CONT rats. Heart and ventricle weights were higher in PRESS and RUN than in CONT rats; body weights were not different. These data suggest that chronic treadmill running results in adaptations that influence cardiovascular and hormonal responses to ICSS.

Animals↗

Exercise increases inflammatory macrophage antitumor cytotoxicity.

This study determined the effects of exercise on the ability of inflammatory macrophages to inhibit tumor cell growth in vitro (macrophage cytotoxicity). Thioglycollate injection (1 ml ip) was used as an inflammatory challenge and to partially activate macrophages for cytotoxicity. Inbred male C3H/HeN mice (n = 180) exercised moderately (MOD, 18 m/min, 30 min/day, 5% grade) or to exhaustion (EXH, 18-35 m/min, 2-4 h, 5% grade) on a motor-driven treadmill for 3 consecutive days after injection. Control (CON) mice were kept in stimulated treadmill lanes directly over the runners. Mice were killed immediately or 3 or 8 h postexercise. Macrophages from both MOD and EXH exercise groups manifested significantly (P < 0.05) enhanced (approximately 50%) cytotoxicity compared with those from CON group at all time points postexercise. This potentially beneficial exercise effect was not related to macrophage production of interleukin-1 beta, reactive nitrogen or oxygen intermediates, or number of macrophages in the assay but may have been manifested, in part, by tumor necrosis factor-alpha. Plasma corticosterone was significantly elevated immediately postexercise in MOD and EXH compared with CON mice; however, no evidence existed for an immuno-suppressive effect of corticosterone on macrophage cytotoxicity, perhaps because of insensitivity of inflammatory macrophages to glucocorticoid suppression seen in vitro. These data only partially support the "inverted U hypothesis," which states that moderate exercise may enhance, whereas very heavy exercise or a lack of exercise may attenuate, the immune response. Further study is needed to determine the physiological significance of these findings and the effects of exercise on macrophage subsets sensitive to glucocorticoid suppression (i.e., fully activated macrophages).

Animals↗

Dose response of prophylactic antipsychotics.

A review of the literature concerning the use of oral and depot antipsychotic medication has high-lighted some important considerations in the treatment of chronic schizophrenic patients. All patients not treated with any form of antipsychotic drug will relapse within 3 years. These relapses will be more clinically significant and will occur at greater frequency than in patients who receive medication on a regular basis. Careful consideration should be given to each patient when choosing between oral or depot medication and inpatient or outpatient therapy. In addition, the clinician should consider the dosage schedule of each medication and balance this against the probability of extrapyramidal side effects and noncompliance. One option for the prevention of relapse without an increase in adverse side effects is the administration of depot haloperidol. For all therapeutic options, medication should be given on a regular basis, since intermittent dosing strategies do not work, and psychosocial rehabilitation should be initiated.

Administration, Oral↗

Weekly variability in total body water using 2H2O dilution in college-age males.

The variability in measuring total body water (TBW) using deuterium oxide (2H2O) dilution has not been extensively tested. The purpose of this study was to determine the variability of weekly measurements of TBW utilizing the 2H2O dilution technique in 10 males and to determine the amount of biological versus technical variability using a generalizability ANOVA (GENOVA). Ten male subjects aged 21-32 yr were tested on four separate occasions for body weight (BW), underwater weight (UwWt), and TBW. BW remained quite stable across the four sessions with a 0.7% coefficient of variation (CV). Both UwWt and TBW had a CV of 4% across the four sessions. No differences were found between TBW estimates from plasma, saliva, or urine. GENOVA analysis determined that 25-50% of the total variability in measuring TBW was attributed to the sample analysis/separation procedures. Four percent of the TBW in these subjects was 1.8 l. This technique would therefore not be expected to detect changes less than 0.9 l (50% of 1.8 l). The estimates of %FAT from TBW were lower but not significantly different from UwWt. Blood, urine, and saliva were able to produce similarly repeatable measures of TBW.

Adult↗

Effects of high- vs moderate-intensity exercise on natural killer cell activity.

The effect of 45 min of high- (80% VO2max) vs moderate- (50% VO2max) intensity treadmill exercise on natural killer cell cytotoxic activity (NKCA) was investigated in 10 well-conditioned (66.0 +/- 1.9 ml.kg-1.min-1), young males (22.1 +/- 1.3 yr). Blood samples were taken before and immediately after exercise, with three more samples taken during 3.5 h of recovery, and analyzed for proportion of NK cells (CD3-CD16+CD56+) and NKCA. Exercise at 80% vs 50% VO2max resulted in a greater immediate postexercise increase in proportion of NK cells, followed by a 1-h and 2-h decrease below preexercise levels for both intensity conditions. NKCA rose significantly above preexercise levels following high- but not moderate-intensity exercise. For both exercise intensity conditions, NKCA tended to drop below preexercise levels by 1 h postexercise, rising back to preexercise levels by 3.5 h postexercise. When NKCA was expressed on a per-NK cell basis, however, no change relative to preexercise levels occurred following moderate-intensity exercise, while a significant increase occurred after 2-h recovery from high-intensity exercise. These data demonstrate that both high- and moderate-intensity exercise are associated with significant shifts in circulating proportions of NK cells which significantly influence interpretation of NKCA data based on assays using separated mononuclear cells.

Adolescent↗

A quantitative analysis of clinical drug trials for the treatment of affective disorders.

This article presents a metaanalysis of approximately 300 studies of drug treatment for affective disorders. Efficacy is proven beyond a shadow of a doubt in this overview from random-assignment, double-blind studies. The efficacy of maintenance antidepressants is supported by a large body of evidence. The size effect of drug versus placebo difference used to prevent recurrence of unipolar or bipolar affective disease is comparable to the size effect of drug versus placebo difference for the treatment of an acute episode.

Antidepressive Agents↗

Respirable industrial fibres: pathology in animal models.

This paper discusses the general efficacy of the rat as a model for studying the pathogenicity of respirable fibres in humans. Rats show differences in lung structure from man and these could influence the pulmonary response to some degree, but they do develop interstitial fibrosis, carcinoma and mesothelioma when exposed to respirable fibres and these same types of lesions are found in fibre-exposed humans. Because of the importance of long fibres in causing pathological change, a substantial number of long respirable fibres must be used in inhalation studies if the relative pathogenicity of different fibre types is to be assessed. From data on the fibre burden in human disease and information on build-up of fibres in rat studies in a range of different fibres, a 1 year exposure to a cloud of 200 fibres ml-1 minimum, preferably more, is recommended. The rate of dissolution of the fibres within the lung milieu will be an an important factor in determining the pathogenicity. Many questions remain unanswered as to the mechanism of lung pathogenicity caused by respirable fibres particularly in the areas of durability, fibre shape, fibre surface chemistry and the exact mechanism, at the cellular level whereby fibres can cause pathological change. The use of rat inhalation studies, properly conceived and designed, remain a key approach whereby these questions can be answered.

Air Pollutants, Occupational↗